Biology Reference
In-Depth Information
related, most of them possessing a common motif of 7 transmembrane domains
(Bockaert and Pin, 1999; Yokoyama and Starmer, 1996). A multitude of human
genes encoding G-protein-coupled receptor with unknown ligands are also
known and these are widely scattered around the genome, for example
GPR1
(15q21.6),
GPR2
(17q21),
GPR3
(1p34-p36),
GPR4
(19q13),
GPR5
(3p21),
GPR6
(6q21-q22),
GPR7
(10q11-q21),
GPR8
(20q13),
GPR9
(8p11-p12),
GPR10
(10q25-q26),
GPR12
(13q12),
GPR13
(3p21-pter),
GPR15
(3q11-q13),
GPR18
(13q32),
GPR20
(8q24).
Heat shock genes.
The heat shock proteins are evolutionarily ubiquitous ('uni-
versal') proteins that function as molecular chaperones under both physiological
and stress conditions. These proteins recognize and stabilize partially folded pro-
teins during the processes of translation, translocation across membranes and
multimer assembly.
Escherichia coli
possesses one heat shock protein gene (
dnaK
),
yeast possesses nine as does
Drosophila
. This superfamily can be subdivided into
three major classes based upon the molecular weight and degree of homology of
the proteins
.
The most highly conserved class is the HSP70 family represented in human by
at least eleven genes:
HSPA1A
,
HSPA1B
and
HSPA1L
linked on chromosome
6p21,
HSPA2
(14q24),
HSPA3
(chromosome 21),
HSPA4
and
HSPA9
linked on
chromosome 5q31,
HSPA5
(9q34),
HSPA6
and
HSPA7
linked on chromosome
1q, and
HSPA8
(11q23-q25). Some members of the HSP70 family are ubiqui-
tously expressed, others are tissue-specific, some are constitutively expressed,
others are expressed only in response to stress (Günther and Walter, 1994). The
HSP70 proteins also differ in their subcellular localization, for example cytosol,
nucleus, nucleolus, endoplasmic reticulum, mitochondrion (Günther and Walter,
1994). The HSP70 genes are extremely ancient having arisen before the diversifi-
cation of cellular life into bacteria, archaebacteria and eukaryotes. Indeed,
sequence data from these proteins have been used to argue for the origin of
eukaryotes via a fusion between archaebacteria and gram-negative bacteria (Gupta
and Golding, 1993; Gupta and Singh, 1994). Not surprisingly in view of their uni-
versality, they exhibit extreme evolutionary conservation (Boorstein
et al
., 1994).
Chromosomal localization has also been conserved evolutionarily as evidenced by
the linkage of three HSP70 genes to the HLA/MHC complex in both humans and
rodents.
The 90 kDa heat shock proteins comprise a second family of evolutionarily
highly conserved proteins which have counterparts in bacteria as well as in all
eukaryotes. Phylogenetic analysis has suggested that the first of the HSP90 gene
duplications occurred very early on in the evolution of the eukaryotes (Gupta,
1995). Human homologues of this gene family are dispersed in the genome and
include
HSPCA
(1q21-q22) and
HSPCB
(6p12). The human genome also con-
tains a group of heat shock proteins of molecular weight 15-30 kDa which are
highly conserved and evolutionarily related to the
-crystallins (de Jong
et al
.,
1993; see Section 4.2.1). Interestingly, one of the human genes encoding heat
shock protein 27 (
HSPB2
) is closely linked to the
-B-crystallin (
CRYAB
) gene
on chromosome 11q22-q23.
